title: In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid.
abstract: OBJECTIVE
  A large-scale, prospective, randomized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduces the incidence of major coronary events. Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules.
  
  
  RESULTS
  A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 (VCAM-1) and nuclear translocation of nuclear factor-kappaB p65 in EPA-treated mice relative to vehicle-treated groups. In an in vitro adhesion assay system under physiological flow conditions, EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules. We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA (1.8 g daily). Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1.
  
  
  CONCLUSIONS
  This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro.
authors.affiliation: Department of Molecular Medicine and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Yamada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Nakano
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Noriko
authors.initials: N
authors.lastname: Satoh
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mita
authors.forename: Kosuke
authors.initials: K
authors.lastname: Azuma
authors.forename: Michiko
authors.initials: M
authors.lastname: Itoh
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy; D051379:Mice; D018613:Microscopy, Confocal; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009765:Obesity / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D011446:Prospective Studies; D051996:Transcription Factor RelA / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015118:Eicosapentaenoic Acid